An important role for retinoids in cancer prevention and therapy has been demonstrated by a wide variety of research including clinical studies. Despite major advances in the study of both the regulatory and molecular mechanisms involved in the action of various retinoids, fundamental questions remain concerning many basic aspects of the metabolism of these compounds. A major focus of our work in the retinoids area has been to better understand how control mechanisms involved in retinoid metabolism are operating. We have begun a series of retinoid turnover studies using rats to investigate the effects of diet and synthetic retinoid upon normal vitamin A (retinol) metabolism. Our initial studies have involved supplementation of normal diets and diets low in vitamin A content with the retinoid 4-hydroxyphenyl retinamide (4-HPR). Graphical analysis of the plasma concentration curves revealed that the plasma levels of retinol were more than five times lower in the 4-HPR supplemented group as compared to the controls. The apparent utilization of retinol was decreased about 75% in 4-HPR supplemented animals as compared to control animals, while at the same time the 4-HPR group increased the fraction of its plasma retinol being used per day by nearly one and a half times. Retinol remained in the plasma for shorter periods and remained sequestered in tissues for longer periods in the 4-HPR supplemented groups. Thus far it would appear that 4-HPR is affecting retinol kinetics and overall tissue metabolism in a very different manner than other synthetic retinoids.